Autoregulation of human cardiac homeobox gene CSX1: mediation by the enhancer element in the first intron.
Csx/Nkx-2.5 is a murine homeobox gene expressed predominantly in cardiocytes and their progenitor cells. The highly lineage-restricted expression pattern of Csx/Nkx-2.5 gene suggests the existence of a positive autoregulatory loop in the transcriptional regulation of Csx/Nkx-2.5. The first intron of CSX1, a human homolog of Csx/Nkx-2.5 gene, had two potential CSX1-binding sequences. Activity of the CSX1 minimal promoter in cultured cardiac myocytes was significantly increased by placing the 3' half of the CSX1 first intron downstream of the reporter gene, suggesting that this region functions as a positive enhancer element. Transient transfection experiments in nonmuscle cells demonstrated that the reporter construct containing the CSX1 minimal promoter and the 3' half of the CSX1 first intron was strongly transactivated by overexpression of CSX1, whereas the CSX1 minimal promoter alone was not. Together these results suggest that the highly lineage-restricted expression of CSX1 is accomplished by autoactivation, which may be mediated by the enhancer element in the first intron.
Oka
T
T
Department of Medicine III, University of Tokyo School of Medicine, Japan.
Komuro
I
I
Shiojima
I
I
Hiroi
Y
Y
Mizuno
T
T
Aikawa
R
R
Akazawa
H
H
Yamazaki
T
T
Yazaki
Y
Y
D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005091:Exons; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D017930:Genes, Reporter / Q000235:genetics; D016678:Genome; D006321:Heart / Q000196:embryology / Q000502:physiology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006706:Homeostasis; D006801:Humans; D007438:Introns; D014157:Transcription Factors; D014158:Transcription, Genetic
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors